PROJECT SUMMARY The broad, long-term objective of this proposal is to enable a better understanding of the inorganic signatures of life and the fundamental interaction of metals in biology that underlie metal homeostasis and human diseases as well as improving metal-based cancer therapeutics and diagnostics. This will be accomplished via the acquisition of a new Laser Ablation Inductively Coupled Plasma Time-of-Flight Mass Spectrometer (LA-ICP- TOF-MS). There is currently one, 10-year-old laser ablation system at Northwestern University whose long washout and acquisition times and limited resolution sensitivity are hindering advanced metallomics and bioinorganic research. Funds are requested for the purchase of an LA-ICP-TOF-MS that will play a vital role in supporting basic and preclinical research activities from multiple NIH-funded and Investigator-Initiated Projects at Northwestern University. As a shared resource, the proposed instrumentation will also support NIH-funded projects from other institutions especially regional partners such as the University of Chicago and the University of Illinois at Chicago. The analytical capabilities offered by the new LA-ICP-TOF-MS will enable quantitative mapping of elemental distribution in biological samples down to 1 m resolution and increase analysis and scan rates more than 5-fold over the current system. The seamless integration of the major system components along with significant advances in mapping software will enable investigators to truly begin to map the metallome and advance understanding of the fundamental properties of metals in biology. LA-ICP-TOF-MS analysis will benefit current research projects in advanced molecular imaging, biomarker development, oocyte maturation, nanoparticle design, and clinical research. The availability of this system will also foster new collaborations and spur instrumentation and application development. To accommodate this instrument, the University has made concrete commitments in terms of financial support, analytical expertise, management, operational staff and infrastructure. The LA-ICP?TOF-MS will become an important component in the Quantitative Bio-element Imaging Center (QBIC) and the Chemistry of Life Processes Institute at Northwestern University. Overall, investigative approaches offered by the LA-ICP-TOF-MS system will enable high resolution, high throughput, quantitative elemental mapping that address the technological needs of the current user base and accelerate a wide range of biomedical research project